Imaging infection with compounds that bind to thymidine kinase

Abstract

The instant invention provides a method for diagnosing an infection in a subject by administering to the subject a compound suitable for imaging which binds to a thymidine kinase present in the infecting organism, and obtaining an image of the subject to determine the presence and location of the compound, wherein a localization of the compound is indicative that the subject has an infection.

1. A method for diagnosing a bacterial infection in a subject comprising:
 administering to the subject a compound suitable for imaging which binds to an endogenous bacterial thymidine kinase present in the infecting bacteria; and 
 obtaining an image of the subject to determine the presence and location of the compound; wherein a localization of the compound is indicative that the subject has a bacterial infection wherein the compound is a radiolabeled nucleoside. 
 
     
     
       2. The method of  claim 1 , wherein the image of the subject is acquired by a method selected from the group consisting of planar gamma imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET). 
     
     
       3. The method of  claim 1 , wherein the nucleoside analog is labeled with radioactive fluorine or iodine. 
     
     
       4. The method of  claim 3 , wherein the compound is selected from the group consisting of 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([125I]-FIAU), 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([124I]-FIAU), 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG), (18)F-1-(2′-deoxy-2′-fluoro-beta-d-arabinofuranosyl)thymine ([18F]-FMAU), 18F-2′-fluoro-2′deoxy-1beta-D-arabinofuranosyl-5-ethyl-uracil ([18F]-FEAU) and 1-(2′-deoxy-2′-fluoro-beta-D-arabinofuranosyl)-5-[18F] iodouracil ([18F]-FIAU). 
     
     
       5. The method of  claim 1 , wherein the nucleoside analog emits gamma particles. 
     
     
       6. The method of  claim 1 , wherein the nucleoside analog is fluorescent. 
     
     
       7. The method of  claim 1 , wherein the bacterial infection is caused by bacteria from a genus selected from the group consisting of  Escherichia, Bacillus, Chromobacterium, Clostridium, Enteroccus, Haemophilus, Listeria, Mycoplasma, Pasteruella, Salmonella, Staphylococcus, Streptococcus, Streptomyces, Vibrio , and  Yersinia.    
     
     
       8. A method for imaging a bacterial infection in a subject comprising:
 administering to the subject a compound suitable for imaging which binds to an endogenous bacterial thymidine kinase present in the infecting bacteria; and 
 obtaining an image of the subject; 
 thereby obtaining an image of the bacterial infection in a subject wherein the compound is a radiolabeled nucleoside. 
 
     
     
       9. The method of  claim 8 , wherein the image of the subject is acquired by a method selected from the group consisting of planar gamma imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET). 
     
     
       10. The method of  claim 8 , wherein the compound is selected from the group consisting of 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([125I]-FIAU), 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([124I]-FIAU), 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG), (18)F-1-(2′-deoxy-2′-fluoro-beta-d-arabinofuranosyl)thymine ([18F]-FMAU), 18F-2′-fluoro-2′deoxy-1beta-D-arabinofuranosyl-5-ethyl-uracil ([18F]-FEAU) and 1-(2′-deoxy-2′-fluoro-beta-D-arabinofuranosyl)-5-[18F] iodouracil ([18F]-FIAU). 
     
     
       11. The method of  claim 8 , wherein the nucleoside analog emits gamma particles. 
     
     
       12. The method of  claim 8 , wherein the nucleoside analog is fluorescent. 
     
     
       13. The method of  claim 8 , wherein the compound suitable for imaging is an antibacterial compound. 
     
     
       14. The method of  claim 8 , where the method allows for the differentiation of bacterial infection and inflammation. 
     
     
       15. The method of  claim 14 , wherein the compound is an antibacterial, antiviral, or antifungal compound. 
     
     
       16. A method for imaging bacterial-based anticancer therapy comprising:
 administering to a subject a compound suitable for imaging which binds to an endogenous bacterial thymidine kinase present in a therapeutic bacteria; and 
 imaging the subject to determine the presence and location of the compound; 
 thereby imaging a bacterial-based anticancer therapy wherein the compound is a radiolabeled nucleoside. 
 
     
     
       17. The method of  claim 16 , wherein the image of the subject is acquired by a method selected from the group consisting of planar gamma imaging, single photon emission computed tomography (SPECT) and positron emission tomography (PET). 
     
     
       18. The method of  claim 16 , wherein the nucleoside analog is labeled with radioactive fluorine or iodine. 
     
     
       19. The method of  claim 18 , wherein the compound is selected from the group consisting of 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([125I]-FIAU), 2′-fluoro-2′deoxy-1-beta-D-arabinofuranosyl-5-iodo-uracil ([124I]-FIAU), 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG), (18)F-1-(2′-deoxy-2′-fluoro-beta-d-arabinofuranosyl)thymine ([18F]-FMAU), 18F-2′-fluoro-2′deoxy-1beta-D-arabinofuranosyl-5-ethyl-uracil ([18F]-FEAU) and 1-(2′-deoxy-2′-fluoro-beta-D-arabinofuranosyl)-5-[18F] iodouracil ([18F]-FIAU). 
     
     
       20. The method of  claim 16 , wherein the nucleoside analog emits gamma particles. 
     
     
       21. The method of  claim 16 , wherein the nucleoside analog is fluorescent.